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Vonk, J.M.* ; Scholtens, S.* ; Postma, D.S.* ; Moffatt, M.F.* ; Jarvis, D.* ; Ramasamy, A.* ; Wjst, M. ; Omenaas, E.R.* ; Bouzigon, E.* ; Demenais, F.* ; Nadif, R.* ; Siroux, V.* ; Polonikov, A.V.* ; Solodilova, M.* ; Ivanov, V.P.* ; Curjuric, I.* ; Imboden, M.* ; Kumar, A.* ; Probst-Hensch, N.* ; Ogorodova, L.M.* ; Puzyrev, V.P.* ; Bragina, E.Y.* ; Freidin, M.B.* ; Nolte, I.M.* ; Farrall, A.M.* ; Cookson, W.O.C.M.* ; Strachan, D.P.* ; Koppelman, G.H.* ; Boezen, H.M.*

Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium.

PLoS ONE 12:e0172716 (2017)
Publ. Version/Full Text Research data DOI
Open Access Gold
Creative Commons Lizenzvertrag
Background Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma. Methods We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overallinteraction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects. Results First approach: 50 SNPs were selected based on an overall interaction effect at p<10-4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63∗10-5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10-4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21∗10-4; replication: ORint = 1.40, p = 0.03). Conclusions Using two genome-wide interaction approaches, we identified novel polymorphisms in nonannotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Whole-genome Association; Environment Interaction; Childhood Asthma; Human-diseases; Large-scale; Exposure; Decline; Egea
ISSN (print) / ISBN 1932-6203
Journal PLoS ONE
Quellenangaben Volume: 12, Issue: 3, Pages: , Article Number: e0172716 Supplement: ,
Publisher Public Library of Science (PLoS)
Publishing Place Lawrence, Kan.
Reviewing status Peer reviewed